Mcmanuscrowley3384
n pregnant women.Telmisartan (TEL) is an antihypertensive BCS class II drug with low solubility at physiological pH. However, the solubility of TEL increases with the presence of an alkalizer. Electrospinning is one of the most recent techniques for the solubility enhancement studies. In this study, an electrospun orally disintegrating film (ODF) formulation of TEL was developed with L-arginine and polyvinylpyrrolidone K90 (PVP), and its characterization studies were performed. Preformulation studies were performed to investigate possible incompatibilities in the components of formulation with differential scanning calorimetry (DSC) and Fourier transform infrared spectrometer (FT-IR) analyses. ODFs were characterized in terms of drug content and uniformity, mechanical properties, fiber shape and diameter and in vitro dissolution profile. Smooth nanofibers without any beads were obtained. The dissolution rate of the TEL significantly increased. The chosen formulation had acceptable mechanical properties with much faster dissolution compared to the commercially available product. Developed ODF and marketed product were compared with a dissolution study in phosphate-buffered solution (pH 7.4). ODF and marketed product both reached 100% release in the 45th minute, and ODF results showed that ODF had much faster release than marketed product. In this study, TEL ODF formulation was successfully produced and characterized.Alzheimer's disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to earein; P-tau - hyperphosphorylated tau protein; RMP - reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA - single-molecule array; ThT - thioflavin T; TSEs - Transmissible Spongiform Encephslopathies; T-tau - total tau protein.
To evaluate the feasibility and clinical value of fetal left modified myocardial performance index (Mod-MPI) in assessment and management of prenatal twin anemia polycythemia sequence (TAPS).
We retrospectively reviewed fetuses with TAPS diagnosed prenatally between 2015 and 2019 at Asan Medical Center. Doppler ultrasound evaluation including the peak systolic velocity (PSV) of the middle cerebral artery (MCA) and fetal echocardiography including left Mod-MPI were evaluated and followed up after antenatal management.
Among 10 cases of fetal twin pregnancies with prenatal TAPS, six were spontaneous and four were post-laser TAPS. Left Mod-MPI was abnormal in one or both twins of nine cases (90%) including all post-laser TAPS (
= 4) and 83.3% of spontaneous TAPS (
= 5). Three recipients, one donor and three former recipients/new donors had elevated left Mod-MPI values, and one donor, one recipient, two former donors/new recipients had decreased values. Antenatal intervention was performed in eight casefor assessment of compromised fetal cardiac function in cases with prenatal TAPS. Application of fetal left Mod-MPI in prenatal staging of TAPS might help evaluate the severity of TAPS and decide timely antenatal intervention.Introduction Rare bleeding disorders (RBDs) are a heterogeneous group of bleeding disorders. Consanguineous marriage is the favorite partnership in many communities among a population of more than a billion. Consanguineous marriages allow the defective recessive genes in RBDs to remain in the family. Clinical approach to RBDs is not as straightforward as typical bleeding disorders, which are secondary to scarcity and variation of RBDs. However, in many developing countries, the limitations of diagnostic facilities, the supply of therapeutic coagulation concentrates, health budgets, and optimal health-care infrastructures may intensify the clinical practice of RBDs.Areas covered The author addresses the role of consanguineous marriage in the incidence of RBDs and what preventive steps can be considered to minimize the incidence of RBDs. A literature review of PubMed and google Scholar was conducted in November of 2020 using the relevant keywords.Expert opinion This review addresses the prevalence of consanguineous marriages in Middle Eastern countries and the various reasons behind the coexistence of consanguineous marriage with RBDs. Finally, prevention steps that may be considered by health-care systems to minimize the incidence of rare bleeding disorders have been discussed. Health-care systems should train partners with the intention of consanguineous marriage on the downside of consanguinity.
Systemic sclerosis (SSc) is an autoimmune disease caused by the imbalance between the activity of angiotensin II and angiotensin-(1-7). Their balance should be controlled by angiotensin-converting enzyme 2 (ACE2), which degrades angiotensin II into angiotensin-(1-7). Previously, autoantibodies to ACE2 (anti-ACE2) were identified in patients with vasculopathy due to different connective tissue diseases, including SSc, but their frequency in SSc was not further analyzed. The aim of the research was to investigate the prevalence and potential role of those anti-ACE2 antibodies in SSc patients.
There were enrolled 27 patients with SSc and 23 healthy donors. ELISA assay determined the presence of anti-ACE2 autoantibodies in serum samples. The results were compared to plasma measurements of angiotensin-(1-7) level
commercial ELISA.
The presence of anti-ACE2 autoantibodies was confirmed in five patients with SSc and two healthy controls. Two of those SSc subjects were anti-Scl70+, another two were double ana Ang-(1-7).Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanying memory deficits. The available pharmaceutical care has some limitations mostly entailing side effects, shelf-life, and patient's compliance. The momentous implications of nutraceuticals in AD have attracted scientists. Several preclinical studies for the investigation of nutraceuticals have been conducted.Areas covered This review focuses on the potential use of a nutraceuticals-based therapeutic approach to treat and prevent AD. click here Increasing knowledge of AD pathogenesis has led to the discovery of new therapeutic targets including pathophysiological mechanisms and various cascades. Hence, the present contribution will attend to the most popular and effective nutraceuticals with proposed brief mechanisms entailing antioxidant, anti-inflammatory, autophagy regulation, mitochondrial homeostasis, and more. Therefore, even though the effectiveness of nutraceuticals cannot be dismissed, it is essential to do further high-quality randomized clinical trials.Expert opinion According to the potential of nutraceuticals to combat AD as multi-target directed drugs, there is critical importance to assess them as feasible lead compounds for drug discovery and development. To the best of the authors' knowledge, modification of blood-brain barrier permeability, bioavailability, and features of randomized clinical trials should be considered in prospective studies.
Dysregulation of RNA binding proteins (RBPs) has been identified in multiple malignant tumors correlated with tumor progression and occurrence. However, the function of RBPs is not well understood in hepatocellular carcinoma (HCC).
The RNA sequence data of HCC was extracted out of the Cancer Genome Atlas (TCGA) database and different RBPs were calculated between regular and cancerous tissue. The study explored the expression and predictive value of the RBPs systemically with a series of bioinformatic analyzes.
A total of 330 RBPs, including 208 up-regulated and 122 down-regulated RBPs, were classified differently. Four RBPs (MRPL54, EZH2, PPARGC1A, EIF2AK4) were defined as the forecast related hub gene and used to construct a model for prediction. Further study showed that the high-risk subgroup is poor survived (OS) compared to the model-based low-risk subgroup. The area of the prognostic model under the time-dependent receiver operator characteristic (ROC) curve is 0.814 in TCGA training group and 0.729 in validation group, indicating a strong prognostic model. We also created a predictive nomogram and a web-based calculator (https//dxyjiang.shinyapps.io/RBPpredict/) based on the 4 RBPs and internal validation in the TCGA cohort, which displayed a beneficial predictive ability for HCC.
Our results provide new insights into HCC pathogenesis. The 4-RBP gene signature showed a reliable HCC prediction ability with possible applications in therapeutic decision making and personalized therapy.
Our results provide new insights into HCC pathogenesis. The 4-RBP gene signature showed a reliable HCC prediction ability with possible applications in therapeutic decision making and personalized therapy.Introduction Molecular technology has played an important role in arboviruses diagnostics. PCR-based methods stand out in terms of sensitivity, specificity, cost, robustness, and accessibility, and especially the isothermal amplification (IA) method is ideal for field-adaptable diagnostics in resource-limited settings (RLS).Areas covered In this review, we provide an overview of the various molecular methods for West Nile, Zika, Dengue and Chikungunya. We summarize literature works reporting the assessment and use of in house and commercial assays. We describe limitations and challenges in the usage of methods and opportunities for novel approaches such as NNext-GenerationSequencing (NGS).Expert opinion The rapidity and accuracy of differential diagnosis is essential for a successful clinical management, particularly in co-circulation area of arboviruses. Several commercial diagnostic molecular assays are available, but many are not affordable by RLS and not usable as Point-of-care/Point-of-need (POC/PON) such as RReal-TimeRT-PCR, Array-based methods and NGS. In contrast, the IA-based system fits better for POC/PON but it is still not ideal for the multiplexing detection system. Improvement in the characterization and validation of current molecular assays is needed to optimize their translation to the point of care.
Semaphorin4D (Sema4D), a novel integral membrane glycoprotein, plays a role in atherosclerosis, angiogenesis and chronic inflammation. Elevated levels of sema4D were presented in myocardial infarction, heart failure and atrial fibrillation. Aim of the study was to investigate the relation between sema4D and recurrence after catheter ablation (CA) in paroxysmal AF.
The present study included 161 paroxysmal AF patients (PAF) (101 patients undergone CA) and 60 healthy subjects. Serum levels of sema4D were measured and study participants were followed-up for 3 months and 1 year since CA in terms of recurrence respectively.
Sema4D levels were significantly elevated in the recurrent group compared to the non-recurrent PAF patients (
< 0.001). Sema4D was importantly positively correlated with both left atrial volume index (
= 0.51,
< 0.013) and high sensitive C-reactive protein (
= 0.38),
< 0.011). In multivariate analysis, sema4D [odds ratio (OR) = 1.23, 95% CI 1.11-1.42;
< 0.001] and left atrial diameter (OR = 1.
